Our prospective studies of >6,000 children showed about all acquire primary HHV infection by 3 years, resulting in 20% of emergency room visits, 13% of hospitalizations, and is the most frequent cause of febrile seizures. Continued studies showed 2 important findings: (1) HHV6 congenital transmission occurs in 1% of births, the same as for cytomegalovirus (CMV). (2) HHV6 congenitally infected infants have different viral and clinical characteristics than those with postnatal infection, and are somewhat similar to those of congenital CMV infection. We thus hypothesize that infants with congenital HHV6 infection have a distinctive course and outcome from infants with postnatal infection, and congenital HHV6 infection results in an adverse effect on the control of HHV6 infection and on the child's neurodevelopmental outcome. Hence, we Aim (I) to determine the virologic course of HHV6 in infants with congenital versus postnatal infection and (II) the neurodevelopmental outcome of congenital HHV6 infection. Two cohorts of children, those with congenital and postnatal infection, will be obtained from the obstetrical centers in the Rochester Strong Health System (7400-7800 births/year) by presence or absence of HHV6 DNA in cord bloods. 237-265 infants with cord bloods DNA positive and 237-265 matched infants with negative cord bloods will be followed over 4 years at 2 weeks, 4, 6, 12-15, and 24-30 months. Samples of cord and peripheral bloods, saliva, and urine will be evaluated to delineate the relative persistence of HHV6 infection, its replicative state (latent or productive), and viral load. HHV6 IgG and neutralizing antibody levels and cellular immunity for Thl and Th2 cytokine responses to tetanus will be measured. These combined assays will allow comparison of each cohort's ability to control HHV6 infection. In Aim II, we will determine if congenital HHV6 infection, like CMV, results in progressive neurodevelopmental impairments by evaluating the 2 cohorts at 2 weeks, 4, 6, 12-15, and 20-30 months by audiologic testing and neurodevelopmental assessments which are sensitive, tailored for young infants, and delineate specific neurodevelopmental areas and growth curves. Thus specific areas of impairment may be detected which could be missed with global measurements. Correlation of these measurements with the viral and clinical characteristics in Aim I may allow early identification of risk factors that are predictive of future disabilities.